The construction of genetic maps is an important aspect of the Human Genome project, particularly for the practical application of localizing disease genes in affected families. The tedious and slow RFLP method of data generation for constructing genetic maps is quickly being superseded by PCR-based analysis of VNTRs such as CA repeats and tri-nucleotide repeats. Using such methods, the rate-limiting step is not data generation, but instead data analysis: the highly informative yet complex nature of the data requires careful, time-consuming, error-prone inspection and interpretation by the investigator. We have recently made strides in the automation of CA repeat data acquisition and analysis using fluorescently-labeled multiplexed CA repeats. The PCR products are analyzed on an automated sequencer, and the digital data are automatically analyzed and interpreted by novel algorithms; the results can then be presented to via custom user interfaces. Our goal is to fully mechanize such PCR-based genotyping of families: small blood samples enter the system, and, without human intervention, the computer-based system performs all requisite processing, analysis, and presentation of results. The proposed system would automate both gene mapping and gene localization, and be applicable to any human chromosome. Starting from a well-characterized 2.5 megabase X-linked gene, we specifically propose to develop an automation system that localizes disease genes anywhere on the X chromosome.